6-78867669-A-C

Position:

• chr6-78867669-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001010844.4(IRAK1BP1):​c.93A>C​(p.Arg31Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IRAK1BP1 NM_001010844.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.831

Genes affected

IRAK1BP1 (HGNC:17368): (interleukin 1 receptor associated kinase 1 binding protein 1) Predicted to be involved in I-kappaB kinase/NF-kappaB signaling. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03625536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRAK1BP1	NM_001010844.4	c.93A>C	p.Arg31Ser	missense_variant	1/4	ENST00000369940.7	NP_001010844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRAK1BP1	ENST00000369940.7	c.93A>C	p.Arg31Ser	missense_variant	1/4	1	NM_001010844.4	ENSP00000358956	P1
IRAK1BP1	ENST00000606868.5	c.63A>C	p.Arg21Ser	missense_variant, NMD_transcript_variant	1/5	1		ENSP00000475570

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.93A>C (p.R31S) alteration is located in exon 1 (coding exon 1) of the IRAK1BP1 gene. This alteration results from a A to C substitution at nucleotide position 93, causing the arginine (R) at amino acid position 31 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.45
DANN	Benign	0.43
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.015
Sift	Benign	0.77	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.27		Loss of methylation at R31 (P = 0.0258);
MVP		0.095
MPC		0.068
ClinPred		0.086	T
GERP RS		-7.0
Varity_R		0.11
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-79577386;